This is a revision of application number 1 R01 A149744-01. The human T lymphotropic viruses types 1 and 2 (HTLV-I, HTLV-II) co-infect 5-1 0 percent of HIV-infected individuals, especially in metropolitan areas where intravenous drug use is a mode of acquisition. Evidence from human studies and from comparative studies in nonhuman primates suggests that the composite effect of HIV/HTLV co-infection is increased HTLV-I/II viral replication and viral burden. This may accelerate the risk for neurodegenerative disease, lymphoproliferative syndromes and other HTLV-associated diseases. In this project the virologic, hematologic, clinical features and substance abuse patterns associated with HIV/HTLV co-infections will be characterized. The clinic population will include over 250 co-infected individuals at the New Orleans HIV Outpatient Clinic. Our patient cohort is one of the largest in the United States. We will determine the relationship between HIV and HTLV-I/II viral burden and (1) past and present patterns of illicit drug use, (2) clinical and neurologic manifestations of disease, (3) rates of CD4 and CD8 decline, (4) development of AIDS and (5) expression HTLV-I/II -associated illnesses in dually infected patients. Comparisons will be made with over 2,500 patients infected with HIV-1 alone, using information extracted from the Adult Spectrum of Disease Clinical Database. Existing clinical specimens available in a specimen repository and freshly obtained blood specimens will be used to determine the relationship between HTLV-I/II virus expression in peripheral blood mononuclear cells and expression of clinical disease. The ultimate goal of this project is to define the dynamics of HIV/HTLV co-infections as a necessary step in disease staging and devising appropriate treatments.